Dr. Jung aims to develop novel preclinical models and therapeutic strategies that can be immediately applied to clinical trials in the field of brain cancer. He focuses on developing new anti-cancer drug targets and precision medicine models by using computational analyses and patient-derived samples of malignant gliomas. In particular, he is interested in the mechanisms that contribute to chemotherapy resistance, including tumoral intra/inter-heterogeneity, the tumor microenvironment, cancer stem cells, and so on.

He found that NIX, a mitochondrial autophagy receptor, was over-expressed in the pseudopalisading cells that envelop hypoxic-necrotic regions, and that mitochondrial NIX expression was robust in patient-derived glioblastoma tumor tissues and glioblastoma stem cells (GSCs). The clinical significance of these findings was validated by a significant association between expression levels and poor outcomes for glioblastoma patients. This indicated that the NIX-mediated mitophagic pathway may represent a key therapeutic target for solid tumors, including glioblastoma.

Dr. Jung’s work has provided insights into the relationship between metabolic dysregulation and epigenetic modification in tumor cells, and how they hijack this relationship to drive cancer. For example, Dr. Jung discovered that a critical node in methyl donor metabolism, an enzyme called nicotinamide N-methyltransferase (NNMT), ranked among the most consistently overexpressed metabolism genes in glioblastoma relative to normal brains. This indicates that NNMT is a GSC-specific therapeutic target in glioblastoma by disrupting oncogenic DNA hypomethylation.

More recently, Dr. Jung has been investigating how dopamine receptor D2 (DRD2) signaling pathways are mechanistically linked to epigenetic regulation—and DRD2 antagonism is beneficial for cancer therapies, including those treating gliomas. In this research project, Dr. Jung examined a potential linkage between protein dimerization of a dopamine receptor and histone methylation in specific subtypes of glioblastoma. Underscoring the potential clinical importance of this work, he contributed to a clinical trial at the NCI Center for Cancer Research’s Neuro-Oncology Branch (NOB) that is based on preclinical studies of a DRD2 inhibitor. Overall, Dr. Jung’s work has had a great impact on translating studies from bench to bedside in the neuro-oncology field.